Chikungunya virus (CHIKV) as an arbovirus transmitted by mosquitoes, causes CHIKV disease with a spectrum of acute clinical symptoms. The development of a specific and highly sensitive detection tool is urgently crucial for early diagnosis and clinical treatment. Herein, a novel sandwich-type electrochemical immunosensor (STEM) was designed, where prussian blue (PB) was in situ generated on tungsten disulfide (WS2) as a highly efficient signal probe, while Zr-metal-organic framework (UiO-66-NH2) and Ti3C2Tx MXene served as the substrate materials. In principle, the large specific surface area of MOFs facilitated the immobilization of biorecognition elements, as well as the excellent conductivity of Ti3C2Tx could achieve signal amplification. Moreover, WS2@PB synergistically offered electrochemical signals, enabling the indirect quantitative detection of CHIKV antigen (CHIKV-Ag). Benefiting from the advantages of the nanocomposite materials, this strategy demonstrated an extensive linear range (0.05-1000 ng & sdot;mL-1) via differential pulse voltammetry with a low detection limit (5.0 pg & sdot;mL-1). Hence, this work presents a new electrochemical immunosensing platform for rapid CHIKV detection, and offers a potential direction for the diagnosis of arboviruses.
Pulmonary diseases caused by Mycobacterium avium complex (MAC) show species-specific epidemiology: M. avium predominates in HIV-positive patients, while M. intracellulare mainly affects immunocompetent hosts. This study aimed to elucidate the bacterial and host mechanisms underlying these differences. We integrated clinical metagenomic next-generation sequencing (mNGS), k-mer-based bacterial genome-wide association study (GWAS) of clinical isolates, peripheral blood immunophenotyping of 175 patients, and mouse infection models with or without CD4 depletion. K-mer GWAS identified lipid metabolism and transport genes (notably mce) enriched in isolates from hosts with different HIV statuses. Immunophenotyping showed that in HIV-negative patients, M. intracellulare infection elicited higher NKT cell frequencies than M. avium, a difference absent in HIV-positive hosts. In mice, anti-CD4−/M. intracellulare infection showed steadily increasing bacterial burden with time (ρ = 0.824), whereas M. avium exhibited no such trend. Early after infection (weeks 1–2), anti-CD4−/M. avium group had higher bacterial burden and NKT levels than anti-CD4−/M. intracellulare, but by week 4 the pattern reversed (all p < 0.05). CD4 depletion eliminated species-specific differences in NKT activation, and at both weeks 2 (p < 0.05) and 4 post-infection (p > 0.05), the anti-CD4+/M. avium groups carried a higher bacterial burden than the anti-CD4+/M. intracellulare groups. MAC species exhibit fundamentally divergent infection dynamics driven by differential NKT cell activation, likely shaped by species-specific lipid antigens. This lipid-NKT axis explains contrasting clinical patterns of M. avium and M. intracellulare and highlights a potential target for host-directed interventions.
The role of marginal zone B (MZB) cells in SARS-CoV-2 immunity remains unclear, particularly in comparing vaccine-induced responses to natural infection. MZB cells are crucial for rapid antibody responses, but their contributions to vaccine-induced immunity, especially in the elderly, are not fully understood. MZB-deficient (FcµR-/-) mice were immunized with SARS-CoV-2 spike protein-conjugated virus-like particles (VLPs). B cell receptor repertoire (BCR) profiles and antibody levels were assessed using ELISA, flow cytometry and single-cell sequencing. Human peripheral blood samples were collected from vaccinated individuals and unvaccinated elderly patients with Omicron infection. Vaccinated blood samples were collected at four time points: Pre-vaccine, Post-2nd dose (7 days), 6 months post-2nd, Post-booster (7 days). Infected patient samples were collected during acute and recovery phases. All samples were analyzed using hypersensitive chemiluminescence immunoassays, protein microarrays and flow cytometry. MZB cell deficiency in mice reduced splenic BCR repertoire diversity. In vaccinated individuals, total SARS-CoV-2 antibodies, including IgG, IgM and RBD-ACE2 competitive neutralization surrogate response peaked at Post-2nd dose (7 days), declined at Post-2nd dose (7 days), and increased significantly at Post-booster (7 days). Protein microarray analysis confirmed vaccine-induced antibodies targeting RBD and spike proteins. Significant expansion was observed in the percentage of MZB cells (CD21+CD23-) and follicular helper T cells (Tfh, ICOS+CXCR5+) at Post-booster (7 days), accompanied by a decrease in the percentage of follicular B cells (FoB, CD21-CD23+) in PBMCs. In contrast, unvaccinated elderly Omicron-infected individuals showed increased MZB cells during recovery compared to acute infection. MZB cells contribute to humoral immunity after both SARS-CoV-2 vaccination and natural infection. The delayed immune response in elderly individuals with natural infection underscores the importance of prioritizing vaccination for timely protection in this vulnerable group.
Urine metabolomics plays a crucial role in biomarker discovery and disease monitoring, but challenges in metabolite preservation remain. This study evaluates the use of styrene divinylbenzene reversed phase sulfonate (SDB-RPS) disks for enriching and preserving urine metabolites utilizing ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) for analysis. We compared SDB-RPS-enriched urine samples with untreated urine across three experimental parts: (1) metabolic profiling using C18 and HILIC chromatography under both positive and negative ion modes; (2) degradation kinetics, where SDB-RPS and untreated urine samples were incubated at 55, 65, and 75 °C with constant humidity (75%); and (3) disease classification using hepatitis (n = 72) and cirrhosis (n = 72) samples. The results revealed that metabolite identification was highly consistent between SDB-RPS and urine samples, with an overlapping rate of 88.26%. Additionally, in the disease classification task, the SDB-RPS panel demonstrated consistent performance, with AUC values of 0.867 and 0.828 in training and validation data sets, respectively, outperforming the urine panel (AUC: 0.765 and 0.691, respectively). These findings suggest that SDB-RPS disks significantly enhance the enrichment and long-term preservation of urine metabolites, offering a promising tool for clinical sample analysis and biomarker discovery.
Fluorine 18 ([18F])–labeled DPA-714 binds to the translocator protein (TSPO), which can be used for monitoring activated glial cells during inflammatory process, and be potentially helpful for localizing the epileptogenic zone. In this study, we aimed to analyze the application of [18F] DPA-714 PET in preoperative evaluation of epilepsy, and to validate the results through surgical outcome and pathological results. Patients who underwent epilepsy surgery with both preoperative [18F]DPA-714 PET and 18F-fluorodeoxyglucose ([18F]FDG) PET were retrospectively reviewed. We visually compared [18F]DPA-714 PET, [18F]FDG PET findings and clinical data. The asymmetry index (AI) were also analyzed for both PET modalities. Pathological correlations with TSPO-positive findings ([18F]DPA-714 PET positive regions) were assessed using CD68 antibodies to identify microglial cells. Eight patients were included in this study. All patients were seizure-free after one-year follow-up. Three patients underwent resection of regions that showed increased uptake on [18F]DPA-714 PET. These three patients had temporal lobe resection or temporal and opercular epileptogenic lesion resection, and their [18F]DPA-714 PET results showed hypermetabolism in ipsilateral mesial temporal lobe. We compared the microglial cells density in the gray matter and white matter separately, and found that microglial cells density was higher in the mesial temporal regions ([18F]DPA-714 PET positive regions) than in the anterior lateral temporal regions ([18F]DPA-714 PET negative regions) in both gray matter (p = 0.003) and white matter (p < 0.001). [18F]DPA-714 PET was more restricted than [18F]FDG PET in patients with temporal lobe epilepsy by visual analysis, whereas [18F]FDG PET showed greater asymmetry in frontal lobe epilepsy. The [18F]DPA-714 PET positive regions correlated with increased microglial density, and it showed a different sensitivity in the recognition of the epileptogenic lesions in temporal and frontal lobe epilepsy.
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has become the predominant cause of liver diseases, with a rising incidence globally, has gained considerable attention. As a heterogeneous disease, it imposes a significant economic burden on society and can progress to severe outcomes like cirrhosis, hepatocellular carcinoma (HCC) and even death. However, awareness, attention, and early intervention for MASLD are lacking, as the disease often starts insidiously and remains asymptomatic in its initial stages. The traditional diagnostic approaches, including liver biopsy and routine laboratory tests, are limited by their invasiveness, acceptance, and specificity. Similarly, imaging methods struggle with high costs and insufficient sensitivity. Early diagnosis and management of MASLD are critical to preventing the onset and decelerating the progression of liver fibrosis, thereby improving liver health. These challenges have prompted considerable efforts to develop non-invasive tests for diagnosing and managing MASLD. Using serum alone or in combination with imaging technology has the potential to improve early diagnostic accuracy, allowing clinicians to better assess and classify the disease. This article offers a comprehensive overview of the current state of non-invasive assessments for MASLD, discussing their applicability and exploring their potential in diagnosing and staging steatosis, MASH, and fibrosis, thereby enhancing patient management and care.
The emergence of various SARS-CoV-2 variants presents challenges for antibody therapeutics, emphasizing the need for more potent and broadly neutralizing antibodies. Here, we employed an unbiased screening approach and successfully isolated two antibodies from individuals with only exposure to ancestral SARS-CoV-2. One of these antibodies, CYFN1006-1, exhibited robust cross-neutralization against a spectrum of SARS-CoV-2 variants, including the latest KP.2, KP.3 and XEC, with consistent IC50 values ranging from ~1 to 5 ng/mL. It also displayed broad neutralization activity against SARS-CoV and related sarbecoviruses. Structural analysis revealed that these antibodies target shared hotspot but mutation-resistant epitopes, with their Fabs locking receptor binding domains (RBDs) in the "down" conformation through interactions with adjacent Fabs and RBDs, and cross-linking Spike trimers into di-trimers. In vivo studies conducted in a JN.1-infected hamster model validated the protective efficacy of CYFN1006-1. These findings suggest that antibodies with cross-neutralization activities can be identified from individuals with exclusively ancestral virus exposure.
Background: Taxane-based chemotherapy is the primary treatment for triple-negative breast cancer (TNBC), yet clinical outcomes remain unsatisfactory due to the persistence of chemoresistance. Identifying key factors that contribute to chemoresistance and understanding the associated molecular mechanisms is therefore essential. Method: The GEO databases were utilized to pinpoint factors related to chemoresistance, which were subsequently validated using clinical tissue samples. The role of UGCG in the malignant progression and chemoresistance of TNBC was assessed through various functional assays. Western blotting, qRT-PCR, and immunohistochemistry were employed to investigate the signaling pathways associated with UGCG in TNBC. Results: UGCG expression was notably elevated in chemoresistant breast cancer tissues and cells, as identified in GEO databases and confirmed through immunohistochemistry. Additionally, findings from our cohorts indicated that higher levels of UGCG expression correlated with a lower rate of pathological complete response (pCR), suggesting it could serve as an independent predictor of chemotherapy effectiveness. Gain- and loss-of-function experiments demonstrated that UGCG enhanced the proliferation, metastasis, and stemness of breast cancer cells. Furthermore, treatment with paclitaxel or docetaxel resulted in increased UGCG expression, which in turn reduced chemotherapy-induced cell apoptosis and improved drug resistance and metastatic capabilities. Mechanistically, UGCG was found to amplify the activation of NF-κB and Wnt/β-catenin pathways, and the use of inhibitors targeting these pathways diminished the UGCG-induced malignant effects. Conclusion: Our findings underscore the significant role of UGCG in the chemoresistance and progression of breast cancer, suggesting it as a predictive biomarker and potential therapeutic target to combat chemoresistance in this disease.
Background:The composition of lung flora in HIV-combined community-acquired pneumonia (CAP) populations may be associated with the duration and severity of the disease. Additionally, a correlation may exist between lung flora balance and the body's autoimmune status. However, the number of studies in this area is limited. Therefore, we collected alveolar lavage fluid from 110 HIV-positive CAP patients at Beijing Ditan Hospital. We preliminarily explored the lung flora of this population using 16S amplicon analysis, and found some clues about the relationship between flora and immune status by comparing the flora of two groups of people with different immune status. Results:We found that the lung microbiome of HIV patients with CAP exhibited a "high-level aggregation-low-level dispersion" pattern across taxonomic hierarchies, this was characterised by dominant taxa at higher classification levels and dispersed, low-abundant taxa at lower levels. Microbial diversity in the AIDS group (CD4+ counts < 200 cells/μL) was marginally lower than in the HIV group, but the difference was not statistically significant. The AIDS group exhibited increased relative abundances of pathogenic taxa (Gammaproteobacteria, Fusobacteriia) and decreased relative abundances of symbiotic taxa (Bacilli, Cyanobacteriia). LEfSe revealed significant enrichment of oral- and gut-associated microbial communities in the HIV group, as opposed to pathogen-enriched communities in the AIDS group. Microbial network analysis showed enhanced modularization in the AIDS group, with reduced clustering coefficients and network density, indicating destabilized microbial communities. Immune collapse appeared to drive a shift from cooperative hub-based to competitive modular microbial structures. Conclusions:Immune status profoundly influenced the composition and function of the pulmonary microbiome in HIV infection. AIDS patients exhibited pathogen-dominated, less stable microbial communities. These findings provided foundational insights into interactions among HIV, CAP, and the pulmonary microbiome, and informed the development of microbiome-targeted interventions.
Objective:This study aimed to identify autophagy-related genes (ARGs) with prognostic significance in hepatocellular carcinoma (HCC) using bioinformatics and survival analysis. Materials and Methods:ARGs were sourced from multiple references, including the Human Autophagy Database (HADb), relevant literatures, the Gene Set Enrichment Analysis (GSEA), and a final list was confirmed after eliminating duplicate entries. Differential expression analysis between normal and tumor tissues relied on data from The Cancer Genome Atlas (TCGA). Subsequently, the univariate and multivariate Cox regression analysis, along with the Kaplan-Meier survival analysis, were conducted to identify survival-associated genes. These findings were cross-validated using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database and the Human Protein Atlas (HPA) database. Furthermore, expression levels of randomly selected ARGs were validated in HCC and normal cell lines using Real-time quantitative PCR (RT-qPCR), confirming bioinformatics findings. Results:41 ARGs were pinpointed. The bioinformatics analysis revealed elevated expression levels of these genes in HCC tissues compared to normal tissues. Notably, mRNA expression levels of ARGs were markedly higher in the tumor tissue samples than in the normal liver tissue samples. This observation was corroborated by data from the GEPIA2 and HPA databases, except for ATG4B and CAPN10. Results from the HPA database aligned with those from the TCGA analysis. GSEA uncovered potential signaling pathways associated with ARGs, including pathways relevant to cancer and autophagy. RT-qPCR analysis further confirmed significant upregulation of mRNA expression levels of randomly selected BAG3, EIF2AK2, KIF5B, and RAB24 in HCC cell lines, consistent with the bioinformatics analysis findings. Conclusion:This study showed that the 41 obtained ARGs, such as ATG16L1, ATG4B, BAG3, KIF5B, MAPK1, RAB24, and SOGA1, these findings suggest that ARGs may serve as prognostic biomarkers for HCC, warranting further validation in clinical cohorts and functional studies.
BackgroundHBV infection continues to pose a significant global health challenge, particularly in patients with normal alanine aminotransferase (ALT) level. The increasing prevalence of Metabolic dysfunction-associated steatotic liver disease (MASLD) among individuals with chronic hepatitis B (CHB) also presents new complications in management. The study aimed to investigate the relationship between MASLD and HBV DNA clearance in CHB patients with normal ALT.Methods403 patients with ALT levels below the normal threshold who underwent liver biopsy at our institution and subsequently received antiviral therapy with NAs were retrospectively examined. Among these, 177 patients were diagnosed with MASLD. Further single cell data analysis was conducted on GSE192740 and GSE182159.ResultsCHB patients concurrent with MASLD had a higher probability of achieving HBV DNA clearance. The proportion of CD8+Teff-GZMH cells was increased in the MASLD group. The interactions among CD8+ Trm-CD69 cells and other T cell subtypes were enhanced, especially within the active CCL-CCR pathways. An elevated proportion of Monocyte-THBS1 was also observed.ConclusionsCD8+ Trm-CD69 T cells may be activated by Monocyte-THBS1 cells, thereby stimulating the immune system via the CCL-CCR signaling axis. This activation facilitates the recruitment of immune cells and enhances the clearance of hepatitis B virus (HBV).
KP.3.1.1 became a dominant successor to JN.1 by the second half of 2024 but the intrinsic pathogenicity and virological feature of KP.3.1.1 remain incompletely understood. Here, we comprehensively evaluated the pathogenesis and characteristics of KP.3.1.1 in comparison to JN.1 and other JN.1-derived variants including JN.1.7, KP.2, and KP.3. The unique S31del mutation on KP.3.1.1 spike confers further evasion to the clinically authorized mAb Pemivibart and reduces convalescent serum neutralization efficiency. Structural analysis indicates that S31del induces novel glycosylation sites that facilitates evasion of neutralizing antibodies. We further reveal that S31del significantly enhances pseudovirus entry efficiency in all evaluated cell types including the human primary nasal epithelial cells. Nevertheless, the intrinsic pathogenicity of KP.3.1.1 is similar to JN.1 and KP.3, and higher than that of JN.1.7 and KP.2 in a male hamster model. Interestingly, the increased virus infectivity conferred by S31del in KP.3.1.1 spike is counterbalanced by the NSP10 S33C mutation. Overall, our study indicates that a single spike mutation can confer both enhanced immune escape and increased viral infectivity. The opposing effects of spike and non-spike mutations highlight the complex interplay of viral genomic elements in shaping their overall fitness, and reveal the high plasticity of coronavirus evolution.
The clinical manifestation of COVID-19 after SARS-CoV-2 infection varies greatly, with many patients requiring intensive care due to complications like acute respiratory distress syndrome, reduced respiratory system compliance, and altered iron metabolism, which can be mistaken for worsening Influenza A infection. This highlights the need to study the humoral immune response to better understand the pathophysiology of viral respiratory infections and improve treatments and diagnostics. This study analyzed autoantibody and acute-phase reactant profiles in patients infected with SARS-CoV-2 and Influenza A using customized protein microarrays for sensitive and reproducible results. The findings revealed a significant increase in autoantibodies in SARS-CoV-2 patients, including those targeting calcitonin-related polypeptides, hepatocyte growth factor, or interleukin 8, compared to Influenza A patients, who showed elevated levels of selectin E and surfactant protein D. Additionally, most acute-phase reactants were higher in SARS-CoV-2 patients. The serological profile showed that the wild-type SARS-CoV-2 strain induced both IgM and IgG responses to all viral proteins, while other strains triggered an IgG response only at a later stage. Multiomics factor analysis identified key factors driving variation in COVID-19's heterogeneous disease presentation. These insights offer valuable information for developing vaccines and therapeutic strategies against SARS-CoV-2.
BACKGROUND:The purpose of this study is to explore the common differentially expressed genes (DEGs) between multiple myeloma (MM) and osteoporosis and the associated molecular mechanisms. RESEARCH DESIGN AND METHODS:We obtained the overlapping DEGs between MM and osteoporosis with the GEO2R online tool. Then, the DEGs were clustered on the MetaCore website to identify the biological process and pathway. In addition, the STRING database and Cytoscape were used to construct the protein-protein interaction (PPI) network and identify hub genes. Finally, miRNA-gene and transcriptional factor (TF)-gene interaction networks were constructed. RESULTS:A total of 252 genes were identified as DEGs in the overlapping two datasets. Functional analysis emphasizes the crucial role of the cell cycle in these two diseases. 10 hub genes were identified using cytoHubba, including CCNA2, ASPM, MKI67, FN1, FEN1, STAT1, DEPDC1, ITGB8, DYNC2LI1, HBEGF. In addition, according to the miRNA-gene and TF-gene interaction networks, part of TFs (RELA, TP53), and miRNAs (miR-26b-5p, miR-192-5p) may be identified as key regulators in MM and osteoporosis at the same time. CONCLUSIONS:The present study reveals the common pathogenesis of MM and osteoporosis. These shared pathways may provide new targets for further mechanistic studies of the pathogenesis and treatment of MM and osteoporosis.
Bilateral basal ganglia germinomas are exceptionally rare intracranial germ cell tumors associated with significant diagnostic delays and irreversible neurological impairment. This study addressed this diagnostic challenge by analyzing the largest dedicated cohort of histopathologically confirmed bilateral basal ganglia germinomas (n = 8). We identified alarming diagnostic delays (median, 1.2 years) in 62.5% of cases, culminating in irreversible deficits such as paralysis and cognitive impairment. Key early clinical indicators included adolescent predominance (mean age, 12.4 years), marked male predominance (7:1), cognitive decline (87.5%), and hemiparesis or monoparesis (62.5%). Magnetic resonance imaging detected cerebral atrophy in 87.5% of patients, with 25.0% showing concomitant mass lesions and atrophy, a distinctive radiological pattern not previously emphasized in unilateral basal ganglia germinomas. Cerebrospinal fluid beta-human chorionic gonadotropin analysis demonstrated superior sensitivity to serum testing (57.1% vs 28.6%). To mitigate devastating outcomes, we propose integrated cerebrospinal fluid beta-human chorionic gonadotropin screening combined with magnetic resonance imaging, with an emphasis on atrophy detection. In patients exhibiting progressive deficits or serial radiological progression despite negative biomarker results, stereotactic biopsy should be prioritized to enable early intervention and preserve neurological function.
Background:The clinical manifestations of cerebrovascular disease are known to differ between the Chinese and United States (U.S.) populations as do the plaque features on imaging. Objectives:The aim of this study was to investigate and compare the histological features of excised carotid plaques from Chinese and U.S. patients. Methods:Carotid endarterectomy specimens collected from two prospective studies were included. The entire plaque was serially sectioned (10 μm thickness) at 0.5-1 mm intervals. Hematoxylin and eosin staining and Mallory's trichrome staining were performed. The morphology and components of the plaques were measured and compared between the two groups. Results:A total of 1,152 histological sections from 75 Chinese patients and 1,843 sections from 111 U.S. patients were analyzed. The Chinese group had significantly smaller minimum lumen diameters (median: 1.1 vs. 1.3 mm, p=0.046) and a larger percent wall volume (median: 74% vs. 70%, p=0.018) than the U.S. group. After adjusting for confounding factors, carotid plaques in the Chinese population were more likely to have more lipid pools (β=10.0%, 95%CI: 4.9 to 15.9%), more recent intraplaque hemorrhage (IPH; β=8.4%, 95%CI: 4.5 to 12.7%), and less late IPH (β=-8.2%, 95%CI: -11.3 to -5.4), and fewer fibrous cap disruptions (45% vs. 67%, p=0.061). Chinese plaques were more homogeneous and had a higher percentage of plaques with features of xanthomas than did U.S. plaques (20% vs 2.7%, p<0.001). Conclusions:The histology of Chinese plaques differs significantly from that of U.S. plaques, suggesting substantial differences in the pathophysiology of atherosclerotic cerebrovascular disease between Chinese and North American populations, which could enhance the gap in racial pathology comparison, indicating a need for a different management approach.
Ambient air pollution and systemic inflammation are recognized as risk factors for cardiovascular-kidney-metabolic (CKM) syndrome. However, the joint effect on middle-aged and elderly people in China remains unclear. This research aimed to explore the association between the long-term effects of air pollution/C-reactive protein (CRP) and early CKM syndrome. This cross-sectional cohort involved 9293 participants from the China Health and Retirement Longitudinal Study (CHARLS) in 2015 (Wave 3). The concentrations of air pollutants, including fine particulate matter (PM2.5), inhalable particles (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3) and carbonic oxide (CO), were obtained from the ChinaHighAirPollutants (CHAP), which contains estimates of the concentrations of these air pollutants in residences at the city level. CKM syndrome was diagnosed according to the American Heart Association (AHA) definition, and stages 1 and 2 were defined as early stages in this study. Generalized linear model (GLM) was employed to assess the relationship between air pollutants and CKM syndrome, while the interactions between CRP and air pollutants were also included to evaluate the modified impacts of CRP on the air pollution-CKM association. GLM results revealed that per-SD increases in the concentrations of PM2.5, PM10, SO2, NO2, O3 and CO were corresponded to elevated CKM prevalence, with ORs (95% CI) of 1.209 (1.085-1.346), 1.263 (1.134-1.406), 1.227 (1.098-1.372), 1.182 (1.060-1.317), 1.135 (1.019-1.265) and 1.160 (1.041-1.292), respectively. Stronger correlations were seen among individuals aged ≤ 65 years, males, urban residents and non-smokers. Moreover, CRP was significantly linked to a greater risk of CKM (OR = 1.207, 95% CI 1.126-1.295). Higher concentrations of air pollutants progressively amplified the risk of CKM syndrome associated with elevated CRP. And the adverse effects of air pollutants were most prominent among individuals with moderate, rather than minimal or severe levels of inflammation. Prolonged exposure to air pollutants has been linked to a greater risk of early CKM syndrome, potentially mediated by inflammatory responses. Particularly, CRP modified the air pollutant-CKM relationship in a complex manner, whereas air pollutants showed a more evident modification of the CRP-CKM association. Considering the ageing population and the health burden posed by CKM, interventions should aim to improve air quality and alleviate systemic inflammatory conditions.
Background: Paediatric stroke poses a significant clinical challenge with lifelong disability risks. However, comparative analyses delineating subtype-specific manifestations and outcomes between arterial ischemic stroke (AIS) and haemorrhagic stroke (HS) are lacking. Objective: To characterize and compare the AIS and HS subtypes in a paediatric cohort, focusing on clinical presentation, aetiology, lesion distribution, and outcomes. Methods: This retrospective cohort study included consecutive paediatric patients (1 month-18 years) with first-ever AIS or HS admitted to Beijing Tiantan Hospital between June 2019 and May 2024. Cases were identified through structured electronic medical record review using standardized diagnostic criteria. Results: The cohort comprised 72 paediatric stroke cases (42 AIS, 30 HS) with comparable age distributions (median 8.0 vs 8.5 years) but distinct clinical profiles. While AIS patients predominantly presented with focal deficits (73.8% hemiparesis vs 30.0% in HS), HS cases more frequently exhibited diffuse symptoms, including headache (56.7% vs 11.9%) and nausea/vomiting (36.7% vs 4.8%). Etiological evaluation revealed striking differences: arteriopathies (particularly moyamoya disease and vasculitis) were dominant in AIS, whereas structural vascular anomalies (arteriovenous malformations [AVMs] and cavernomas) were characteristic of HS. At the 12-month follow-up, persistent neurological sequelae were common in both groups (AIS 67.6%, HS 64.3%), though disability patterns diverged; AIS survivors demonstrated predominantly motor deficits (56.8% vs 28.6%) while cognitive impairment was more prevalent in HS (21.4% vs 13.5%). Mortality rates remained low (AIS 2.7%, HS 7.1%), with recurrence observed exclusively in AIS cases (5.4%). Conclusion: Acute paediatric AIS and HS exhibit distinct clinical phenotypes—focal neurological deficits are predominant in AIS versus diffuse symptoms (headache/nausea) in HS, enabling early syndromic differentiation. Despite treatment, persistent neurological morbidity affects >64% of survivors, with subtype-specific disability patterns: AIS is primarily associated with motor impairments, while HS demonstrates greater cognitive sequelae. The low mortality (<7.1%) and recurrence rates reflect advancements in care, yet the enduring disability burden underscores the necessity for subtype-tailored rehabilitation and systematic long-term surveillance.
[This corrects the article DOI: 10.1016/j.crmicr.2025.100480.].
Background/Objectives: Although SARS-CoV-2 infection often follows a self-limiting course, its public health impact remains persistent. Older adults exhibit unique susceptibility to infection due to immunosenescence. Therefore, in order to offer recommendations for improving management options for older persons, this study intends to examine the immunological properties of NAb in the elderly population. Methods: Elderly patients aged 60 years and older infected during the prevalence of BF.7 and EG.5 variants were enrolled. The patterns of NAb responses in infected patients under both natural and vaccine-induced immunity were explored using bead-based proteomics techniques. The associations between NAb and IgG antibody levels, clinical characteristics, and traditional inflammatory indicators were evaluated using systematic analysis. Based on NAb levels, SARS-CoV-2 strains were immunologically classified. Results: There was a positive correlation between the severity of the disease and the strength of the NAb response. Because of more extensive immune activation, severe instances in elderly patients showed higher levels of NAb responses. When compared to the uninfected group, people who had received two doses of vaccination exhibited greater NAb levels. Additionally, there was a link between NAb and IgG levels, but as the virus evolved, this correlation progressively diminished. Three serotypes of SARS-CoV-2 were identified based on NAb response characteristics: pre-Omicron, Omicron, and XBB serotypes. Conclusions: The results show the features of NAb responses in older patients, which could help with the creation of future vaccines and public health initiatives.